The proposed research will investigate methods for prevention of prosthetic valve endocarditis (PVE) caused by the bacterium, Staphylococcus epidermidis, the most common organism causing these infections. The study will involve three phases. In the first phase, the antibiotic susceptibility of isolates from patients with PVE will be determined, mechanisms of antibiotic resistance investigated, and the antibiotic susceptibility characteristics of the organisms related to time of onset of infections following surgery and the antibiotic prophylaxis used in each patient during surgery. In the second phase, antibiotic prophylaxis will be studied using a rabbit model of endocarditis. The value of prophylaxis in preventing infections due to antibiotic-resistant S. epidermidis and in selecting out these resistant isolates will be evaluated. The final phase of the study will be to define the hospital epidemiology of S. epidermidis and the methods of transmission of this organism to patients. Specific markers for hospital-acquired S. epidermidis will be sought using new epidemiologic tools, particularly those which characterize patterns of extrachromosomal DNA.